An Exo III-powered closed-loop DNA circuit architecture for biosensing/imaging.

With their regulated Boolean logic operations in vitro and in vivo, DNA logic circuits have shown great promise for target recognition and disease diagnosis. However, significant obstacles must be overcome to improve their operational efficiency and broaden their range of applications. In this study, we propose an Exo III-powered closed-loop DNA circuit (ECDC) architecture that integrates four highly efficient AND logic gates. The ECDC utilizes Exo III as the sole enzyme-activated actuator, simplifying the circuit design and ensuring optimal performance. Moreover, the use of Exo III enables a self-feedback (autocatalytic) mechanism in the dynamic switching between AND logic gates within this circulating logic circuit. After validating the signal flow and examining the impact of each AND logic gate on the regulation of the circuit, we demonstrate the intelligent determination of miR-21 using the carefully designed ECDC architecture in vitro. The proposed ECDC exhibits a linear detection range for miR-21 from 0 to 300 nM, with a limit of detection (LOD) of approximately 0.01 nM, surpassing most reported methods. It also shows excellent selectivity for miR-21 detection and holds potential for identifying and imaging live cancer cells. This study presents a practical and efficient strategy for monitoring various nucleic acid-based biomarkers in vitro and in vivo through specific sequence modifications, offering significant potential for early cancer diagnosis, bioanalysis, and prognostic clinical applications.

Dye-doped dual-frequency nematic cells as fast-switching polarization-independent shutters.

We present polarization-independent optical shutters with a sub-millisecond switching time. The approach utilizes dual-frequency nematics doped with a dichroic dye. Two nematic cells with orthogonal alignment are driven simultaneously by a low-frequency or high-frequency electric field to switch the shutter either into a transparent or a light-absorbing state. The switching speed is accelerated via special short pulses of high amplitude voltage. The approach can be used in a variety of electro-optical devices.

Polypeptide chain release factor eRF3 is a novel molecular partner of survivin.

The eukaryotic class II polypeptide chain release factor (eRF3) is an eRF1- and ribosome-dependent GTPase involved in translation termination of protein biosynthesis. eRF3 is a multifunctional protein that is also involved in chromosomal segregation and cytokinesis during mitosis. Survivin is a member of the inhibitor of apoptosis protein (IAP) family that is involved in the organisation of spindle and cell apoptosis. Interaction between survivin and eRF3a-F3 or eRF3b, encoded by the GSPT1 and GSPT2 genes, respectively, was confirmed using yeast two-hybrid (Y2H) and pull-down assays in vitro, and co-immunoprecipitation in vivo. The domains involved in the formation of the survivin-eRF3s complex have been identified. The sites on survivin that interact with eRF3 are located in the baculovirus IAP repeat domain (residues 65-76), which forms a beta-strand structure with an overall negative charge. The sites on eRF3 that interact with survivin were localised to the N-terminal domain(NTD; residues 131-200). Cell localisation experiments indicate that both factors are in the nucleus, suggesting that they cooperatively function in nuclear processes.

Nuclear-targeted carbon quantum dot mediated CRISPR/Cas9 delivery for fluorescence visualization and efficient editing.

Nuclear targeted delivery has great potential in improving the efficiency of non-viral carrier mediated genome editing. However, direct and efficient delivery of CRISPR/Cas9 plasmid into the nucleus remains a challenge. In this study, a nuclear targeted gene delivery platform based on fluorescent carbon quantum dots (CQDs) was developed. Polyethylenimine (PEI) and polyethylene glycol (PEG) synergistically passivated the surface of CQDs, providing an excitation-independent green-emitting fluorescent CQDs-PEI-PEG conjugate (CQDs-PP) with an ultra-small size and positive surface charge. Here we show that CQDs-PP could bind CRISPR/Cas9 plasmid to form a nano-complex by electrostatic attraction, which can bypass lysosomes and enter the nucleus by passive diffusion, and thereby improve the transfection efficiency. Also, CQDs-PP could deliver CRISPR/Cas9 plasmid into HeLa cells, resulting in the insertion/deletion mutation of the target EFHD1 gene. More importantly, CQDs-PP exhibited a considerably higher gene editing efficiency as well as comparable or lower cytotoxicity relative to Lipo2000 and PEI-passivated CQDs-PEI (CQDs-P). Thus, the nuclear-targeted CQDs-PP is expected to constitute an efficient CRISPR/Cas9 delivery carrier in vitro with imaging-trackable ability.

Three-dimensional solitary waves with electrically tunable direction of propagation in nematics.

Production of stable multidimensional solitary waves is a grand challenge in modern science. Steering their propagation is an even harder problem. Here we demonstrate three-dimensional solitary waves in a nematic, trajectories of which can be steered by the electric field in a plane perpendicular to the field. The steering does not modify the properties of the background that remains uniform. These localized waves, called director bullets, are topologically unprotected multidimensional solitons of (3 + 2)D type that show fore-aft and right-left asymmetry with respect to the background molecular director; the symmetry is controlled by the field. Besides adding a whole dimension to the propagation direction and enabling controlled steering, the solitons can lead to applications such as targeted delivery of information and micro-cargo.

Electrically driven three-dimensional solitary waves as director bullets in nematic liquid crystals.

Electric field-induced collective reorientation of nematic molecules is of importance for fundamental science and practical applications. This reorientation is either homogeneous over the area of electrodes, as in displays, or periodically modulated, as in electroconvection. The question is whether spatially localized three-dimensional solitary waves of molecular reorientation could be created. Here we demonstrate that the electric field can produce particle-like propagating solitary waves representing self-trapped "bullets" of oscillating molecular director. These director bullets lack fore-aft symmetry and move with very high speed perpendicularly to the electric field and to the initial alignment direction. The bullets are true solitons that preserve spatially confined shapes and survive collisions. The solitons are topologically equivalent to the uniform state and have no static analogs, thus exhibiting a particle-wave duality. Their shape, speed, and interactions depend strongly on the material parameters, which opens the door for a broad range of future studies.

Publisher Correction: Electrically driven three-dimensional solitary waves as director bullets in nematic liquid crystals.

The original version of this article contained an error in the description of Supplementary Movie 7, which incorrectly read 'Collision resulting in annihilation of two solitons. U = 45.1 V, f = 600 Hz, T = 50 °C, d = 8.0 µm. The original movie is taken at the frame rate of 91 fps. The playback speed is 7 fps.' The correct version reads 'Death of a soliton at a dust particle. U = 65.6 V, f = 800 Hz, T = 50 °C, d = 7.7 µm. The original movie is taken at the frame rate of 92 fps. The playback speed is 7 fps.' The HTML has been updated to include a corrected version of the 'Description of Additional Supplementary Files' file.

miRNA-144 suppresses proliferation and migration of colorectal cancer cells through GSPT1.

MicroRNAs play a key role in carcinogenesis or tumor progression, which negatively and posttranscriptionally regulate gene expression and function as oncogenes or tumor suppressors, as well as regulators of cell cycle, proliferation, apoptosis, migration and other processes. A number of miRNAs are reported be related to the occurrence and development of colorectal cancer (CRC). However, these studies were not involved in the effect of miRNA 144 of CRC, whose function remains unclear. In this study, we demonstrated that the expression level of miRNA 144 was markedly down-regulated in colorectal cancer HCT116 cells compared with normal control FHC cells. Meanwhile, we found that GSPT1 was over-expressed in human colorectal cancer HCT116 cells. Subsequently, GSPT1 was identified as a target of miRNA 144 through bioinformatics and luciferase reporter assays. Besides, we also confirmed that miRNA 144 can inhibit the proliferation and migration of colorectal cancer HCT116 cells . Next, we observed RNA-mediated knockdown of GSPT1 can also inhibit the proliferation and migration of colorectal cancer cells. Thus, we concluded that miRNA 144 inhibits cell proliferation and migration through GSPT1 in CRC. In addition, further mechanic investigations revealed that miRNA-144 suppressed the expression of GSPT1 to regulate the expression of c-myc, survivin and Bcl2L15 which are involved in cell proliferation, and that metastasis related factor MMP28 was also down-regulated by miRNA144. Our findings suggested that microRNA 144 might be an important element to control the status of colorectal cancer, which has provided a new insight into the mechanism of proliferation and migration and a new target in therapy against colorectal cancer.